Amino acids and peptides. XVIII. A biogenetic-type, asymmetric synthesis of (S)-reticuline from L-3-(3,4-dihydroxyphenyl)-alanine by 1,3-transfer of asymmetry.

Abstract

The asymmetric synthesis of (S)-reticuline (I) was accomplished by means of the biogenetic-type, asymmetric Pictet-Spengler reaction of 3-(3-hydroxy-4-benzyloxyphenyl)-L-alanine methyl ester hydrochloride (XXIII) with sodium 3-benzyloxy-4-methoxy-phenylglycidate (XXIV) (1, 3-asymmetric induction) and the elimination of the chiral center derived from XXIII (1, 3-transfer of asymmetry), the latter of which was achieved by conversion of the cyclized α-amino acid methyl ester (XXVa) to the N-benzyl α-amino nitrile (XXVIII), followed by reductive decyanization with sodium borohydride. The position of the benzyl group of XXIII which was prepared from L-dopa by monobenzylation was proved by the alternate synthesis of XXIII starting from L-tyrosine. By this success, morphinanedienone, aporphine and protoberberine alkaloids, (-)-pallidine (XXXII), (+)-isoboldine (XXXIII), (-)-coreximine (XXXIV), and (-)-scoulerine (XXXV) are formally to have been synthesized from L-dopa.